The invention relates to a pipetting apparatus with a pipetting head comprising a one-dimensional or two-dimensional arrangement of pipetting channels and an arrangement of releasable pipette tips in communication with the pipetting channels. Each pipetting channel is formed by a plunger and a cylinder, wherein the plungers are guided in the cylinders and are sealed with respect to the cylinders. The cylinder may be provided as a bushing consisting of an elastic material and tightly enclosing the plunger, thereby already achieving a sealing effect. In order to enable a matrix-shaped arrangement of pipetting channels, said bushings are suitably arranged with respect to each other in through bores, e.g. in a rigid plate. The cylinders may also be formed by the through bores of one or more plates arranged above one another. The sealing of the plunger is then usually achieved by additional sealing elements, such as spring-supported rings, sealing sleeves and/or O rings or X rings, respectively.
The cylinders, and thus the pipetting channels, are mounted in a predetermined mutual arrangement pattern in a base plate of the pipetting head. The arrangement pattern usually corresponds to a grid, formed by the intersections of rows and columns disposed perpendicular to each other, with the same grid distance between the axes of the pipetting channels, said grid distance being downwardly limited by a smallest useful diameter of the cylinders and a minimum wall thickness between the cylinders.
The pipette tips are arranged on or around the cylinders in a similar arrangement as the pipetting channels, usually releasable via a seal.
This type of pipetting head and this type of pipetting apparatus are generically known from EP 1,214,977 B1.
Due to the operating principle of the pipetting channels, such pipetting apparatuses are also referred to as air displacement pipettors, air displacement dispensers or air-cushion pipettes.
If it is desired to express the multiplicity rather than the operating principle of the pipetting channels, such pipetting apparatuses are referred to, for example, as simultaneous pipettors, multi-well pipettors, multi-channel dispensers, multi-channel dosage devices, multi-channel pipettes or multi-channel dispensers.
In this type of apparatus, the arrangement pattern, and consequently the spacing and number of the pipetting channels, are usually based on what is called the microtiter plate grid. Typical microtiter plate grids have grid spacings between the axes of the pipetting channels of 9 mm, 4.5 mm, or 2.25 mm and a number of (1), 4, 8, 12, 16, (24, 32, 48) 96, 384 and, in exceptional cases, even 1536 pipetting channels.
Many apparatuses differ further in the way the pipette tips are fastened to and sealed with respect to the pipetting channels.
On the one hand, some devices have complete analogy to hand pipettes, e.g. as described in DE 4 104 831 A1, comprising what is known as receiving cones or receiving shafts (cylindrical or other shape) on which the pipette tips are fitted and sometimes also sealed with what is called an O ring. A device of this type is described in DD 260 571.
On the other hand, there are devices, such as that described in DE 20 2008 013 533 U for example, wherein the sealing surfaces on the end faces of the pipette tips suspended in magazines are jointly pressed against a perforated, plane, elastic sealing mat. This connecting principle between the pipetting channels and the pipette tips has been embodied by the applicant's CyBi-well product family for many years. Pipetting apparatuses with various means for receiving magazines are described, for example, in DE 20 2007 000 904 U and DE 20 2011 000 837 (still unpublished).
The invention described below is applicable to all of the above-mentioned pipetting apparatuses which have exchangeable pipette tips (which is what they are called here) or similarly usable tubes (canulas) or the like. It does not matter whether the pipette tips are so-called disposable articles (injection-molded plastic disposables) or metal, glass or ceramics articles, or reusable plastic articles. Nor does it matter whether the pipetting apparatus is an electro-mechanical or a mechanical pipetting apparatus.
In the practical application of hand pipettes, their users are faced with the everyday situation of selecting the appropriate pipette for the application at hand, usually on the basis of the volume range to be handled. Many laboratories are equipped with pipette stands holding a range of various hand pipettes.
The more channels such a hand pipette has, the more dexterity will be required of its user, and pipettes with 96 or more channels have been properly usable only as standalone devices.
Standalone devices are much more expensive than hand pipettes and also require a lot of space on the lab counter.
Thus, laboratory users are very often faced with the question which pipetting apparatus with what pipetting volume range is the right one. This consideration often leads to the purchase of several apparatuses and, consequently, big investments.
One solution consists in systems with so-called exchangeable heads, i.e. the user buys one basic device and exchangeable pipetting heads.
These devices are optimal for many users because they allow quick and easy re-fitting. One example of such devices is the “CyBi-well vario” system offered by the applicant and described, inter alia, in DE 20 2007 000 904 U. However, due to the required mechanical precision and reliability, such devices are structurally complex, heavy and still expensive.
Moreover, especially when it comes to automatically processable pipetting protocols, it is tedious and unproductive to have to interrupt liquid-handling processes in order to exchange the pipetting heads for the transfer of other volumes.
Several suggestions have been made on how to expand the volume range which can be handled by a pipetting apparatus, i.e. the range between a minimum and a maximum pipettable volume per pipette tip, without exchanging the pipetting head.
DE 41 04 831 A1 describes a pipetting channel (called dosage device in this case) for manual and motor-driven single- and multiple-channel dosage devices, said channel differing from conventional pipetting channels in that it comprises an inner plunger guided within an outer plunger, allowing a large volume to be received in the pipette tip via the plunger stroke of the outer plunger and a small volume to be received in a much more sensitive manner via the plunger stroke of the inner plunger. This solution, known for almost 20 years, requires very complex technology and is still not widely used in practice today.
DE 600 13 983 T2 describes a special pipette tip in which more than only one pipetting channel terminates. The tip may enclose different numbers of pipetting channels or their openings, respectively, depending on the shape and dimensions of the tip collar (called the crown in this case). Such pipette tips have the disadvantage that they must be specially designed, which in turn requires specially shaped and dimensioned seals as well as specially adapted magazines by which the pipette tips can be fitted on the pipetting head.
EP 1,214,977 B1 shows a multi-channel-pipetting apparatus comprising a number of pipetting channels which are connected to pipette tips by an adapter plate such that each pipette tip has at least two pipetting channels assigned to it. Similar to the arrangement pattern of the pipetting channels, the adapter plate comprises a pattern of channel inlets of thinner channels on one side, which are combined in groups inside the adapter to form thicker channels whose outlets are determined by the arrangement pattern of the pipette tips, which corresponds to a microtiter plate grid. This has the particular disadvantage that a pipetting apparatus comprising, for example, 96 pipetting channels, in which the adapter allows to combine, e.g. four pipetting channels each in one pipette tip, can only be pipetted via 24 pipette tips. In other words, the greater the volume to be handled per pipette tip, the smaller will be the number of the pipettable volumes. The enlargement of the pipettable volume is effected, as in accordance with DE 600 13 983 T2, in a linear manner, as a function of the number of pipetting channels connected to each other; in the example just explained, this corresponds merely to a four-fold increase when connecting 4 pipetting channels.